What is the Horvath clock and why is it so well known?

The Horvath clock is a mathematical model that estimates your biological age based on chemical marks at 353 specific locations in your DNA. Those marks, called methyl groups, change in a predictable way as you get older. The model was trained on more than 8,000 tissue samples from 51 different healthy tissues and cell types. That made it the first clock that worked not only in blood, but in virtually every part of the body.

What made the model immediately interesting was an unexpected observation: embryonic stem cells and cells that had been artificially returned to an embryonic state showed a biological age of nearly zero. This suggests that the clock captures something fundamental about cellular 'age', although the precise meaning of this is not yet fully understood. Cancer tissue showed the opposite extreme: on average 36 years more aged than healthy tissue from the same body.

After the Horvath clock, later variants followed, such as PhenoAge and GrimAge. These are better at predicting disease and mortality: they correlate with risk of death, cancer, physical functioning and diseases such as Alzheimer's. The original Horvath clock was less suited to those applications, but it laid the foundation for the entire field.

Researchers also use the clock as a measurement tool in anti-ageing research. For example, mouse studies showed that activating three genes in retinal cells rejuvenated the DNA methylation pattern and partially restored vision loss in glaucoma. The clock made that rejuvenation measurable. There is, however, a clear caveat: there is still no consensus on what a good ageing biomarker should precisely measure, and further validation is needed before it can be used as an endpoint in clinical trials.

On a theoretical level, the Horvath clock has also influenced how researchers understand ageing. It links biological development early in life to the ageing process in later life. Whether the clock measures a cause of ageing or a consequence of it, however, remains an open question.